medwireNews: Erlotinib as first-line therapy in patients with advanced non-small-cell lung cancer (NSCLC) is equivalent to chemotherapy with regard to overall survival, an “all-comers” phase II trial has shown.

The trial also confirmed earlier suggestions that the development of a skin rash is associated with improved survival and that a “dosing to rash” strategy is clinically feasible.

The Eastern Cooperative Oncology Group Study enrolled an unselected cohort of 137 patients with untreated stage IIIB/IV NSCLC. They were treated with erlotinib starting at 150 mg once a day and the dose was escalated by 25 mg every 2 weeks up to 250 mg, unless a grade 2 rash or other dose-limiting toxicity occurred.

Patients who developed a tolerable grade 2 skin rash were maintained on the current dose and no further attempt was made at dose escalation; conversely, if any side effects became intolerable, the dose was reduced in 25 mg increments.

A total of 124 patients completed therapy and were included in the final analysis.

Writing in the European Journal of Cancer, Julie Brahmer (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA) and colleagues report that erlotinib was well tolerated in the first-line setting, with only 24.2% of patients discontinuing treatment due to toxicity and 8.1% refusing treatment.

Two (1%) patients died from treatment-related adverse events (pneumonitis and pulmonary infiltrates). The most common grade 1/2 adverse event was rash, affecting 70% of patients, while the most common grade 3 events were rash, fatigue, and diarrhea, each in 10% of patients.

“Even with dose escalation to a grade 2 rash, not all patients developed a rash,” remark Brahmer et al.

In terms of efficacy, patient response rates and survival were consistent with those seen in other clinical trials of erlotinib. In all, 6.5% of patients had an objective response, 1.6% had a complete response, and 34.7% had stable disease, giving a disease control rate of 41.1%.

The median time to progression was 3.3 months and median overall survival was 7.7 months.

Interestingly, patients who developed a grade 2 or greater rash did not have a better response rate or disease control rate than those who did not; however, these patients had significantly better overall survival, living for 6.8 months longer on average than patients without a rash.

The researchers say their results indicate that erlotinib used as first-line treatment in an unselected population has similar efficacy to that of first-line chemotherapy. Furthermore, “intrapatient dose escalation of erlotinib beyond 150 mg to develop a tolerable rash was feasible.”